Name: Alectinib HCl 
CAS#: 1256589-74-8 (HCl) 
Chemical Formula: C30H35ClN4O2 
Exact Mass: 
Molecular Weight: 519.086 
Elemental Analysis: C, 69.42; H, 6.80; Cl, 6.83; N, 10.79; O, 6.16


EOS Med Chem produce Alectinib,AF 802, CH 5424802, RO 5424802, Alecensa, 1256589-74-8  in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.
Alectinib,AF 802, CH 5424802, RO 5424802, Alecensa, 1256589-74-8  Intermediates, EOS Med Chem have 8; Alectinib,AF 802, CH 5424802, RO 5424802, Alecensa, 1256589-74-8  Impurity we have 10, all from GMP, FDA plant.


Now Alectinib,AF 802, CH 5424802, RO 5424802, Alecensa, 1256589-74-8  DMF document is preparing.
Until 2016, Aug, Alectinib,AF 802, CH 5424802, RO 5424802, Alecensa, 1256589-74-8  more than produced 25kg API, 120kg Intermediates

GMP PRODUCE:

Alectinib;Veliparib;Acalabrutinib;Venetoclax;Sotagliflozin;Ledipasvir;LX1606;Anacetrapib;Abemaciclib 

2016 Mumbai CPHI, Hope to meet!

2016 Barcelona CPHI, Hope to meet!

2016 Korea(한국) CPHI, C40, Welcome!

2016 Shanghai CPHI, W5C47, Welcome!

EOS Med Chem, Medchem is Big

執大象，天下往，往而無害，安平泰

網址: www.eosmedchem.com 

郵箱: gutian@eosmedchem.com; eosmedchem@gmail.com 

辦公室: 0086-531-69905422-806(直通)

攜帶番號 & WhatsApp: +8618653174435

Skype: willgutian

Alectinib Alecensa;RG-7853; RO-5424802; AF-802; CH-5424802 1256580-46-7(free base)
Alectinib Alecensa;RG-7853; RO-5424802; AF-802; CH-5424802 1256589-74-8(HCl)
Alectinib Intermediates Ethyl 2-(4-bromophenyl)-2-methylpropanoate 32454-36-7
Alectinib Intermediates 2-(4-bromophenyl)-2-methylpropanoic acid 32454-35-6
Alectinib Intermediates 2-methyl-2-(4-vinylphenyl)propanoic acid 1256584-72-1
Alectinib Intermediates 2-(4-ethylphenyl)-2-methylpropanoic acid 1247119-83-0
Alectinib Intermediates 2-(4-ethyl-3-iodophenyl)-2-methylpropanoic acid 1256584-73-2
Alectinib Intermediates Tert-butyl 4-(4-ethyl-3-iodophenyl)-4-methyl-3-oxopentanoate 1256584-74-3
Alectinib Intermediates Tert-butyl 6-cyano-2-(2-(4-ethyl-3-iodophenyl)propan-2-yl)-1H-indole-3-carboxylate 1256585-29-1
Alectinib Intermediates 6-cyano-2-(2-(4-ethyl-3-(4-morpholinopiperidin-1-yl)phenyl)propan-2-yl)-1H-indole-3-carboxylic acid 1256584-78-7




Description: Alectinib, also known as AF802, or CH5424802 or RO5424802, is a potent, selective, and orally available ALK inhibitor with a unique chemical scaffold, showing preferential antitumor activity against cancers with gene alterations of ALK, such as nonsmall cell lung cancer (NSCLC) cells expressing EML4-ALK fusion and anaplastic large-cell lymphoma (ALCL) cells expressing NPM-ALK fusion in vitro and in vivo. Alectinib inhibited ALK L1196M, which corresponds to the gatekeeper mutation conferring common resistance to kinase inhibitors, and blocked EML4-ALK L1196M-driven cell growth. Alectinib (as HCl salt) was approved in Dec. 2015.
Synonym: AF 802; AF-802; AF802; CH5424802; CH5424802; CH 5424802; RO5424802; RO 5424802; RO5424802, Alectinib; brand name: Alecensa
IUPAC/Chemical Name: 9-ethyl-6,6-dimethyl-8-(4-morpholinopiperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile hydrochloride
SMILES Code: N#CC1=CC2=C(C=C1)C3=C(C(C)(C)C4=CC(N5CCC(N6CCOCC6)CC5)=C(CC)C=C4C3=O)N2.[H]Cl

Related CAS# 
CAS#1256580-46-7 (Alectinib free base) 
CAS#1256589-74-8 (Alectinib HCl)

1: Ou SH, Weitz M, Jalas JR, Kelly DF, Wong V, Azada MC, Quines O, Klempner SJ. Alectinib induced CNS radiation necrosis in an ALK+NSCLC patient with a remote (7 years) history of brain radiation. Lung Cancer. 2016 Jun;96:15-8. doi: 10.1016/j.lungcan.2016.03.008. Epub 2016 Mar 26. PubMed PMID: 27133743.
2: Tchekmedyian N, Ali SM, Miller VA, Haura EB. Acquired ALK L1152R Mutation Confers Resistance to Ceritinib and Predicts Response to Alectinib. J Thorac Oncol. 2016 Apr 15. pii: S1556-0864(16)30081-8. doi: 10.1016/j.jtho.2016.03.018. [Epub ahead of print] PubMed PMID: 27091190.
3: Aikawa H, Hayashi M, Ryu S, Yamashita M, Ohtsuka N, Nishidate M, Fujiwara Y, Hamada A. Visualizing spatial distribution of alectinib in murine brain using quantitative mass spectrometry imaging. Sci Rep. 2016 Mar 30;6:23749. doi: 10.1038/srep23749. PubMed PMID: 27026287; PubMed Central PMCID: PMC4812395.
4: Dong X, Fernandez-Salas E, Li E, Wang S. Elucidation of Resistance Mechanisms to Second-Generation ALK Inhibitors Alectinib and Ceritinib in Non-Small Cell Lung Cancer Cells. Neoplasia. 2016 Mar;18(3):162-71. doi: 10.1016/j.neo.2016.02.001. PubMed PMID: 26992917; PubMed Central PMCID: PMC4796802.
5: Tanaka H, Taima K, Morimoto T, Nakamura K, Tanaka Y, Itoga M, Takanashi S, Okumura K. Dramatic response to alectinib in a patient of ALK-rearranged lung cancer with poor performance status. BMC Res Notes. 2016 Mar 17;9(1):173. doi: 10.1186/s13104-016-1983-9. PubMed PMID: 26987388; PubMed Central PMCID: PMC4794901.
6: Yoshida T, Hida T, Yatabe Y. Rapid and dramatic response to alectinib in an ALK rearranged non-small-cell lung cancer patient who are critically ill. Anticancer Drugs. 2016 Mar 2. [Epub ahead of print] PubMed PMID: 26938871.
7: Yoshimura Y, Kurasawa M, Yorozu K, Puig O, Bordogna W, Harada N. Antitumor activity of alectinib, a selective ALK inhibitor, in an ALK-positive NSCLC cell line harboring G1269A mutation : Efficacy of alectinib against ALK G1269A mutated cells. Cancer Chemother Pharmacol. 2016 Mar;77(3):623-8. doi: 10.1007/s00280-016-2977-y. Epub 2016 Feb 5. PubMed PMID: 26849637.
8: Gainor JF, Chi AS, Logan J, Hu R, Oh KS, Brastianos PK, Shih HA, Shaw AT. Alectinib Dose Escalation Reinduces Central Nervous System Responses in Patients with Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer Relapsing on Standard Dose Alectinib. J Thorac Oncol. 2016 Feb;11(2):256-60. doi: 10.1016/j.jtho.2015.10.010. Epub 2015 Dec 18. PubMed PMID: 26845119; PubMed Central PMCID: PMC4743545.
9: Takegawa N, Hayashi H, Iizuka N, Takahama T, Ueda H, Tanaka K, Takeda M, Nakagawa K. Transformation of ALK rearrangement-positive adenocarcinoma to small-cell lung cancer in association with acquired resistance to alectinib. Ann Oncol. 2016 May;27(5):953-5. doi: 10.1093/annonc/mdw032. Epub 2016 Jan 24. PubMed PMID: 26811347.
10: Pirker R, Filipits M. Alectinib in RET-rearranged non-small cell lung cancer-Another progress in precision medicine? Transl Lung Cancer Res. 2015 Dec;4(6):797-800. doi: 10.3978/j.issn.2218-6751.2015.03.08. PubMed PMID: 26798590; PubMed Central PMCID: PMC4700226.
11: Fujita S, Masago K, Katakami N, Yatabe Y. Transformation to SCLC after Treatment with the ALK Inhibitor Alectinib. J Thorac Oncol. 2016 Jan 2. pii: S1556-0864(15)00275-0. doi: 10.1016/j.jtho.2015.12.105. [Epub ahead of print] PubMed PMID: 26751586.
12: Alectinib Approved for ALK+ Lung Cancer. Cancer Discov. 2016 Feb;6(2):115. doi: 10.1158/2159-8290.CD-NB2016-001. Epub 2016 Jan 6. PubMed PMID: 26739884.
13: Isozaki H, Ichihara E, Takigawa N, Ohashi K, Ochi N, Yasugi M, Ninomiya T, Yamane H, Hotta K, Sakai K, Matsumoto K, Hosokawa S, Bessho A, Sendo T, Tanimoto M, Kiura K. Non-Small Cell Lung Cancer Cells Acquire Resistance to the ALK Inhibitor Alectinib by Activating Alternative Receptor Tyrosine Kinases. Cancer Res. 2016 Mar 15;76(6):1506-16. doi: 10.1158/0008-5472.CAN-15-1010. Epub 2015 Dec 30. PubMed PMID: 26719536.
14: Shaw AT, Gandhi L, Gadgeel S, Riely GJ, Cetnar J, West H, Camidge DR, Socinski MA, Chiappori A, Mekhail T, Chao BH, Borghaei H, Gold KA, Zeaiter A, Bordogna W, Balas B, Puig O, Henschel V, Ou SH; study investigators. Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, phase 2 trial. Lancet Oncol. 2016 Feb;17(2):234-42. doi: 10.1016/S1470-2045(15)00488-X. Epub 2015 Dec 19. PubMed PMID: 26708155; PubMed Central PMCID: PMC4752892.
15: Jassem J. Alectinib in crizotinib-resistant, ALK-positive NSCLC. Lancet Oncol. 2016 Feb;17(2):134-5. doi: 10.1016/S1470-2045(15)00555-0. Epub 2015 Dec 19. PubMed PMID: 26708154.
16: Tani T, Yasuda H, Hamamoto J, Kuroda A, Arai D, Ishioka K, Ohgino K, Miyawaki M, Kawada I, Naoki K, Hayashi Y, Betsuyaku T, Soejima K. Activation of EGFR Bypass Signaling by TGFα Overexpression Induces Acquired Resistance to Alectinib in ALK-Translocated Lung Cancer Cells. Mol Cancer Ther. 2016 Jan;15(1):162-71. doi: 10.1158/1535-7163.MCT-15-0084. Epub 2015 Dec 18. PubMed PMID: 26682573.
17: Miyamoto S, Ikushima S, Ono R, Awano N, Kondo K, Furuhata Y, Fukumoto K, Kumasaka T. Transformation to small-cell lung cancer as a mechanism of acquired resistance to crizotinib and alectinib. Jpn J Clin Oncol. 2016 Feb;46(2):170-3. doi: 10.1093/jjco/hyv173. Epub 2015 Nov 27. PubMed PMID: 26613679.
18: Ou SH, Ahn JS, De Petris L, Govindan R, Yang JC, Hughes B, Lena H, Moro-Sibilot D, Bearz A, Ramirez SV, Mekhail T, Spira A, Bordogna W, Balas B, Morcos PN, Monnet A, Zeaiter A, Kim DW. Alectinib in Crizotinib-Refractory ALK-Rearranged Non-Small-Cell Lung Cancer: A Phase II Global Study. J Clin Oncol. 2016 Mar 1;34(7):661-8. doi: 10.1200/JCO.2015.63.9443. Epub 2015 Nov 23. PubMed PMID: 26598747.
19: Song Z, Wang M, Zhang A. Alectinib: a novel second generation anaplastic lymphoma kinase (ALK) inhibitor for overcoming clinically-acquired resistance. Acta Pharm Sin B. 2015 Jan;5(1):34-7. doi: 10.1016/j.apsb.2014.12.007. Epub 2015 Jan 24. Review. PubMed PMID: 26579422; PubMed Central PMCID: PMC4629211.
20: Takeuchi K, Togashi Y, Kamihara Y, Fukuyama T, Yoshioka H, Inoue A, Katsuki H, Kiura K, Nakagawa K, Seto T, Maemondo M, Hida T, Harada M, Ohe Y, Nogami N, Yamamoto N, Nishio M, Tamura T. Prospective and clinical validation of ALK immunohistochemistry: results from the phase I/II study of alectinib for ALK-positive lung cancer (AF-001JP study). Ann Oncol. 2016 Jan;27(1):185-92. doi: 10.1093/annonc/mdv501. Epub 2015 Oct 20. PubMed PMID: 26487585; PubMed Central PMCID: PMC4684157.

EOS Med Chem produce Evofosfamide,TH 302, 918633-87-1 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok

Name: Evofosfamide

CAS#: 918633-87-1

Chemical Formula: C9H16Br2N5O4P

Exact Mass: 446.93067

Molecular Weight: 449.04

Elemental Analysis: C, 24.07; H, 3.59; Br, 35.59; N, 15.60; O, 14.25; P, 6.90

Description: Evofosfamide, also known as TH-302, is a hypoxia-activated prodrug consisting of a 2-nitroimidazole phosphoramidate conjugate with potential antineoplastic activity. The 2-nitroimidazole moiety of hypoxia-activated prodrug TH-302 acts as a hypoxic trigger, releasing the DNA-alkylating dibromo isophosphoramide mustard moiety within hypoxic regions of tumors. Normoxic tissues may be spared due to the hypoxia-specific activity of this agent, potentially reducing systemic toxicity. Check for active clinical trials or closed clinical trials using this agent. (NCI).

Synonym: TH302; TH 302; TH-302. Evofosfamide

IUPAC/Chemical Name: Phosphorodiamidic acid, N,N'-bis(2-bromoethyl)-, (1-methyl-2-nitro-1H-imidazol-5-yl)methyl ester.

SMILES Code: O=P(NCCBr)(NCCBr)OCC1=CN=C([N+]([O-])=O)N1C

EOS Med Chem produce Evofosfamide,TH 302, 918633-87-1 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.

Evofosfamide,TH 302, 918633-87-1 Intermediates, EOS Med Chem have 8; Evofosfamide,TH 302, 918633-87-1 Impurity we have 10, all from GMP, FDA plant.

Now Evofosfamide,TH 302, 918633-87-1 DMF document is preparing.

Until 2016, Aug, Evofosfamide,TH 302, 918633-87-1 more than produced 25kg API, 120kg Intermediates

GMP PRODUCE:

Alectinib;Veliparib;Acalabrutinib;Venetoclax;Sotagliflozin;Ledipasvir;LX1606;Anacetrapib;Abemaciclib 

2016 Mumbai CPHI, Hope to meet!

2016 Barcelona CPHI, Hope to meet!

2016 Korea(한국) CPHI, C40, Welcome!

2016 Shanghai CPHI, W5C47, Welcome!

EOS Med Chem, Medchem is Big

執大象，天下往，往而無害，安平泰

網址: www.eosmedchem.com 

郵箱: gutian@eosmedchem.com; eosmedchem@gmail.com 

辦公室: 0086-531-69905422-806(直通)

攜帶番號 & WhatsApp: +8618653174435

Skype: willgutian

Evofosfamide TH-302;HAP-302 918633-87-1

Evofosfamide Intermediates (1-methyl-2-nitro-1H-imidazol-5-yl)methanol 39070-14-9

Evofosfamide Intermediates N,N'-Bis(2-bromoethyl)phosphorodiamidic acid 141025-16-3

According to wikipedia.com, TH-302 is an experimental anticancer agent that is in clinical development at Threshold Pharmaceuticals, Inc. It is activated only at very low levels of oxygen (hypoxia). Such levels are common in human solid tumors, a phenomenon known as tumor hypoxia. TH-302 exploits the activation of a nitroazole prodrug by a process that involves a one electron reduction mediated by ubiquitous cellular reductases such as the NADPH cytochrome P450 to generate a radical anion prodrug (RP). In the presence of oxygen (normoxia) the radical anion prodrug reacts rapidly with oxygen to generate the original prodrug and superoxide (SO). Under the low oxygen conditions of the hypoxic zones in tumors, however, the radical anion prodrug undergoes further irreversible reductions to the hydroxylamine (HA) followed by elimination, releasing the active drug and an azole derivative (AZ).

  

TH-302 started a Phase 1 clinical trial in 2007 in various solid tumors. The Phase 1 trial is a multi-center, open-label, dose-escalation study in patients with solid tumor cancers. The primary objectives of the study are to determine the maximum tolerated dose (MTD) and dose-limiting toxicities of TH-302 in patients with advanced solid tumors and to establish the appropriate dose to be tested in Phase 2 clinical trials. The secondary objectives of the trial include establishing the pharmacokinetics and assessing the anti-tumor activity of TH-302, as measured by objective response rate and duration of response, and to characterize the safety profile. Tumors will be evaluated at baseline and every eight weeks using the Response Evaluation Criteria In Solid Tumors (RECIST) criteria. 

EOS Med Chem produce BI-847325,1207293-36-4 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok

Name: BI-847325

CAS#: 1207293-36-4

Chemical Formula: C29H28N4O2

Exact Mass: 464.2212

Molecular Weight: 464.569

Elemental Analysis: C, 74.98; H, 6.08; N, 12.06; O, 6.89

EOS Med Chem produce BI-847325,1207293-36-4 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.

BI-847325,1207293-36-4 Intermediates, EOS Med Chem have 8; BI-847325,1207293-36-4 Impurity we have 10, all from GMP, FDA plant.

Now BI-847325,1207293-36-4 DMF document is preparing.

Until 2016, Aug, BI-847325,1207293-36-4 more than produced 25kg API, 120kg Intermediates

GMP PRODUCE:

Alectinib;Veliparib;Acalabrutinib;Venetoclax;Sotagliflozin;Ledipasvir;LX1606;Anacetrapib;Abemaciclib 

2016 Mumbai CPHI, Hope to meet!

2016 Barcelona CPHI, Hope to meet!

2016 Korea(한국) CPHI, C40, Welcome!

2016 Shanghai CPHI, W5C47, Welcome!

EOS Med Chem, Medchem is Big

執大象，天下往，往而無害，安平泰

網址: www.eosmedchem.com 

郵箱: gutian@eosmedchem.com; eosmedchem@gmail.com 

辦公室: 0086-531-69905422-806(直通)

攜帶番號 & WhatsApp: +8618653174435

Skype: willgutian

BI-847325 BI-847325 1207293-36-4

BI-847325 Intermediates N-ethylpropiolamide 2682-33-9

BI-847325 Intermediates 6-iodoindolin-2-one 919103-45-0

BI-847325 Intermediates (E)-3-(hydroxy(phenyl)methylene)-6-iodoindolin-2-one 1535204-23-9

BI-847325 Intermediates (E)-6-iodo-3-(phenyl((trimethylsilyl)oxy)methylene)-2-((trimethylsilyl)oxy)-3H-indole

BI-847325 Intermediates (Z)-3-(((4-((dimethylamino)methyl)phenyl)amino)(phenyl)methylene)-6-iodoindolin-2-one 1537909-08-2

Description: BI-847325 is an orally available dual inhibitor of mitogen-activated protein kinase kinase (MEK) and Aurora kinases, with potential antineoplastic activity. Upon oral administration, MEK/Aurora kinase inhibitor BI 847325 selectively binds to and inhibits the activity of MEK, which both prevents the activation of MEK-dependent effector proteins and inhibits growth factor-mediated cell signaling. BI 847325 also binds to and inhibits the activity of the Aurora kinases A, B and C which may disrupt the assembly of the mitotic spindle apparatus, prevent chromosome segregation, and inhibit both cellular division and proliferation in Aurora kinase-overexpressing tumor cells.

Synonym: BI-847325; BI 847325; BI847325.

IUPAC/Chemical Name: (Z)-3-(3-((4-((dimethylamino)methyl)phenylamino)(phenyl)methylene)-2-oxoindolin-6-yl)-N-ethylpropiolamide

SMILES Code: O=C(NCC)C#CC1=CC(NC/2=O)=C(C=C1)C2=C(NC3=CC=C(CN(C)C)C=C3)/C4=CC=CC=C4

1: Schöffski P, Aftimos P, Dumez H, Deleporte A, De Block K, Costermans J,

Billiet M, Meeus MA, Lee C, Schnell D, Goeldner RG, Awada A. A phase I study of

two dosing schedules of oral BI 847325 in patients with advanced solid tumors.

Cancer Chemother Pharmacol. 2016 Jan;77(1):99-108. doi:

10.1007/s00280-015-2914-5. Epub 2015 Dec 9. PubMed PMID: 26650227.

2: Phadke MS, Sini P, Smalley KS. The Novel ATP-Competitive MEK/Aurora Kinase

Inhibitor BI-847325 Overcomes Acquired BRAF Inhibitor Resistance through

Suppression of Mcl-1 and MEK Expression. Mol Cancer Ther. 2015 Jun;14(6):1354-64.

doi: 10.1158/1535-7163.MCT-14-0832. Epub 2015 Apr 14. PubMed PMID: 25873592;

PubMed Central PMCID: PMC4458462.

EOS Med Chem produce Refametinib,RDEA-119,BAY 869766, 923032-37-5 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.

Name: Refametinib

CAS#: 923032-37-5

Chemical Formula: C19H20F3IN2O5S

Exact Mass: 572.00897

Molecular Weight: 572.34

Elemental Analysis: C, 39.87; H, 3.52; F, 9.96; I, 22.17; N, 4.89; O, 13.98; S, 5.60

EOS Med Chem produce Refametinib,RDEA-119,BAY 869766, 923032-37-5 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.

Refametinib,RDEA-119,BAY 869766, 923032-37-5 Intermediates, EOS Med Chem have 8; Refametinib,RDEA-119,BAY 869766, 923032-37-5 Impurity we have 10, all from GMP, FDA plant.

Now Refametinib,RDEA-119,BAY 869766, 923032-37-5 DMF document is preparing.

Until 2016, Aug, Refametinib,RDEA-119,BAY 869766, 923032-37-5 more than produced 25kg API, 120kg Intermediates

GMP PRODUCE:

Alectinib;Veliparib;Acalabrutinib;Venetoclax;Sotagliflozin;Ledipasvir;LX1606;Anacetrapib;Abemaciclib 

2016 Mumbai CPHI, Hope to meet!

2016 Barcelona CPHI, Hope to meet!

2016 Korea(한국) CPHI, C40, Welcome!

2016 Shanghai CPHI, W5C47, Welcome!

EOS Med Chem, Medchem is Big

執大象，天下往，往而無害，安平泰

網址: www.eosmedchem.com 

郵箱: gutian@eosmedchem.com; eosmedchem@gmail.com 

辦公室: 0086-531-69905422-806(直通)

攜帶番號 & WhatsApp: +8618653174435

Skype: willgutian

Refametinib BAY-86-9766; AY-869766; RDEA-119; AR-119 923032-37-5

Refametinib Intermediates (S)-tert-butyldimethyl(oxiran-2-ylmethoxy)silane 123237-62-7

Refametinib Intermediates Butyl cyclopropanesulfonate 83635-12-5

Refametinib Intermediates (S)-butyl 1-(3-((tert-butyldimethylsilyl)oxy)-2-hydroxypropyl)cyclopropane-1-sulfonate 1335100-23-6

Refametinib Intermediates (S)-butyl 1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonate 1335100-30-5

Refametinib Intermediates (S)-butyl 1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)cyclopropane-1-sulfonate 1335100-31-6

Refametinib Intermediates Sodium (S)-1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)cyclopropane-1-sulfonate 1262760-34-8

Refametinib Intermediates (S)-1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)cyclopropane-1-sulfonyl chloride 1262760-00-8

Refametinib Intermediates 2,3,5-trifluoro-N-(3-fluoro-4-iodophenyl)-6-nitroaniline 765962-71-8

Refametinib Intermediates 2,3-difluoro-N-(2-fluoro-4-iodophenyl)-5-methoxy-6-nitroaniline 923032-72-8

Refametinib Intermediates 5,6-difluoro-N1-(2-fluoro-4-iodophenyl)-3-methoxybenzene-1,2-diamine 923032-74-0

Refametinib Intermediates (S)-N-(3,4-difluoro-2-((2-fluoro-4-iodophenyl)amino)-6-methoxyphenyl)-1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)cyclopropane-1-sulfonamide 1262760-18-8

Description: Refametinib, also known as RDEA119, BAY 86-9766, is an orally bioavailable selective MEK inhibitor with potential antineoplastic activity. MEK inhibitor RDEA119 specifically inhibits mitogen-activated protein kinase kinase 1 (MAP2K1 or MAPK/ERK kinase 1), resulting in inhibition of growth factor-mediated cell signaling and tumor cell proliferation. MEK, a dual specificity threonine/tyrosine kinase, is a key component of the RAS/RAF/MEK/ERK signaling pathway that regulates cell growth; constitutive activation of this pathway has been implicated in many cancers.

Synonym: RDEA119; RDEA-119; RDEA 119; BAY 869766; BAY-69766; BAY869766; BAY 86 9766; BAY 86-9766; BAY86-9766; BAY 869766

IUPAC/Chemical Name: (S)-N-(3,4-difluoro-2-((2-fluoro-4-iodophenyl)amino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide

SMILES Code: O=S(C1(C[C@H](O)CO)CC1)(NC2=C(OC)C=C(F)C(F)=C2NC3=CC=C(I)C=C3F)=O

BAY 86-9766, formerly known as RDEA119, is currently being developed by Ardea. BAY 86-9766  is a potent, non-ATP competitive, highly-selective inhibitor of MEK. According to Ardea Inc's website, preclinical and clinical data suggest that BAY 86-9766 has favorable properties, including once-daily, oral dosing, excellent selectivity and limited retention in the brain, which may result in a reduced risk of central nervous system (CNS) side effects at doses expected to be effective, a problem associated with other members of this class of compounds. In addition, BAY 86-9766 has been shown to suppress tumor cell growth in-vitro and in-vivo. Phase 1 data have demonstrated that BAY 86-9766 has a long half-life and favorable pharmacokinetic properties, allowing for once-daily oral dosing. Preclinical in vitro and in vivo oncology studies have demonstrated significant potential synergy across multiple tumor types when BAY 86-9766 is used in combination with other approved anti-cancer therapeutics, including sorafenib (Nexavar®; Bayer HealthCare, Onyx Pharmaceuticals). (source: http://www.ardeabio.com/development-pipeline/cancer.htm ).

1: Wylie-Sears J, Levine RA, Bischoff J. Losartan inhibits endothelial-to-mesenchymal transformation in mitral valve endothelial cells by blocking transforming growth factor-β-induced phosphorylation of ERK. Biochem Biophys Res Commun. 2014 Mar 12. pii: S0006-291X(14)00445-8. doi: 10.1016/j.bbrc.2014.03.014. [Epub ahead of print] PubMed PMID: 24632204.

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